Porous Silicon-Based On-Demand Nanohybrids for Biomedical Applications

Considerable efforts have been made to fabricate nano-sized drug delivery systems (DDS) with unique and advanced features in comparison to conventional DDS. Yet, challenges still lay ahead requesting for more controllable, even on-demand drug release profiles from the DDS. Moreover, the emerging concept of personalized treatment further urges the combining of therapy and imaging regimes into a single nanocarrier.Among all the nanomaterials studied so far, porous silicon (PSi) draws increasing interest for constructing DDS due to its good biocompatibility, non-immunogenicity, large pore size/surface area and easily changeable surface properties. Herein, the aim of this thesis was to explore PSi-based DDS for multiple biomedical applications, which were designed and synthesized with specific on-demand features. Moreover, simultaneous incorporation of imaging modalities and drugs enables real-time visualization of drug release and/or cellular/tissue level disease condition, which are expected to be beneficial for personalized treatment regime.First, the potential of PSi nanoparticles for hydrophilic drug loading and on-demand release were evaluated by adapting a dynamic non-covalent bonding method. Different ligands were synthesized and applied for modifying the PSi, and the hydrophilic anti-cancer drug doxorubicin (DOX) was sequentially loaded into the fabricated DDS for pH-responsive release profiles. Meanwhile, the fluorescence spectrum of DOX can be dynamically shifted or quenched, depending on the loading and releasing process, thus facilitating the in situ visualization of the drug releasing process.For hydrophobic drugs, a physical encapsulation method was applied to seal the pores of the PSi by a polymeric matrix. Microfluidic-assisted nanoprecipitation method was applied to synthesize batches of nanohybrids with identical PSi-core/polymer-shell structures, and the release behavior was feasibly tailored by the degradation behavior of the outer polymeric matrix. The first trial was set to fabricate a core/shell nanohybrid, with PSi and gold nanoparticles co-encapsulated in a pH-responsive polymer to simultaneously deliver hydrophobic drug and increase the computed tomography signal for acute liver failure theranostics. The newly established single-step co-encapsulation of different particles endowed a system with multi-functionalities, and the polymeric shell precisely tailored the drug release behavior in a pH-dependent manner. Similarly, an acid/oxidation dual-responsive polymer was designed and further applied in encapsulating atorvastatin-loaded PSi nanoparticles. The meticulously designed system not only obtained a dynamic drug release behavior, but also showed an orchestrated cascade that facilitated bio-mimetic diabetic wound healing. To better elucidate the biocompatibility of PSi for DDS fabrication, the biological effects and immunogenicity of different PSi nanoparticles were evaluated at pre-existing lesion sites, which provided insights for further applications of PSi in DDS fabrication.In conclusion, multiple PSi-based nanohybrids with different on-demand responses were fabricated and applied as DDSs for different diseases. The newly developed nanosystems tailored drug release and obtained multiple modalities, ranging from real-time bio-imaging to bio-mimetic/bio-response alteration, as such, represent promising platforms for future therapy regimes.